Plk2 promotes tumor growth and inhibits apoptosis by targeting Fbxw7/Cyclin E in colorectal cancer.

Polo-like kinase 2 (Plk2) and Polo-like kinase 3 (Plk3) have been documented as a tumor suppressor and are lowly expressed in several types of cancer. However, our results showed that Plk3 was lowly expressed, whereas Plk2 expressed highly in tumor tissues. We therefore aimed to explore the mechanisms governing the role of Plk2 in colorectal cancer (CRC). Our investigation demonstrated that Plk2 was an independent prognostic marker in CRC patients. Plk2 promotes tumor growth and inhibits apoptosis of CRC cells in vitro and in vivo. Moreover, Plk2 binds to Fbxw7 and results in its subsequent degradation, which in turn leads to the stabilization of Cyclin E. The pro-tumor activity of Plk2 could be inverted by restoring Fbxw7 expression and depletion of Cyclin E. In addition, the expressions of Fbxw7 and Cyclin E were significantly associated with Plk2 protein levels in CRC tissues. In conclusion, our data show that Plk2 represents an independent prognostic marker and regulates tumor growth and apoptosis by targeting Fbxw7/Cyclin E pathway in CRC, suggesting Plk2 as a potential therapeutic target.

Ou B ，Zhao J ，Guan S ，Wangpu X ，Zhu C ，Zong Y ，Ma J ，Sun J ，Zheng M ，Feng H ，Lu A ... -  《-》

Tazarotene-induced gene 1 interacts with Polo-like kinase 2 and inhibits cell proliferation in HCT116 colorectal cancer cells.

Tazarotene-induced gene 1 (TIG1) is considered to be a tumor suppressor gene that is highly expressed in normal or well-differentiated colon tissues, while downregulation of TIG1 expression occurs in poorly differentiated colorectal cancer (CRC) tissues. However, it is still unclear how TIG1 regulates the tumorigenesis of CRC. Polo-like kinases (Plks) are believed to play an important role in regulating the cell cycle. The performance of PLK2 in CRC is negatively correlated with the differentiation status of CRC tissues. Here, we found that PLK2 can induce the growth of CRC cells and that TIG1 can prevent PLK2 from promoting the proliferation of CRC cells. We also found that the expression of PLK2 in CRC cells was associated with low levels of Fbxw7 protein and increased expression of cyclin E1. When TIG1 was coexpressed with PLK2, the changes in Fbxw7/cyclin E1 levels induced by PLK2 were reversed. In contrast, silencing TIG1 promoted the proliferation of CRC, and when PLK2 was also silenced, the proliferation of CRC cells induced by TIG1 silencing was significantly inhibited. The above research results suggest that TIG1 can regulate the tumorigenesis of CRC by regulating the activity of PLK2.

Wang CH ，Lu TJ ，Wang LK ，Wu CC ，Chen ML ，Kuo CY ，Shyu RY ，Tsai FM ... -  《-》

Plk2 regulates centriole duplication through phosphorylation-mediated degradation of Fbxw7 (human Cdc4).

Cizmecioglu O ，Krause A ，Bahtz R ，Ehret L ，Malek N ，Hoffmann I ... -  《-》

FBXW7 acts as an independent prognostic marker and inhibits tumor growth in human osteosarcoma.

Li Z ，Xiao J ，Hu K ，Wang G ，Li M ，Zhang J ，Cheng G ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》

Recombinant human adenovirus-p53 injection induced apoptosis in hepatocellular carcinoma cell lines mediated by p53-Fbxw7 pathway, which controls c-Myc and cyclin E.

Tu K ，Zheng X ，Zhou Z ，Li C ，Zhang J ，Gao J ，Yao Y ，Liu Q ... -  《PLoS One》